Sex hormone-binding globulin is associated with androgen deficiency features independently of total testosterone

ObjectiveIt is recognized that total testosterone (TT) does not sufficiently describe androgen status when sex hormone-binding globulin (SHBG) is altered. However, in humans, evidence supporting the existence of a hypogonadism due to low T bioactivity is scanty. The aim of the study was to assess whether changes in SHBG levels, independently of TT, are associated with subjective and objective androgen-dependent parameters. DesignCross-sectional observation. PatientsTwo thousand six hundred and twenty-two men (aged 51.113.5years) attending a Sexual Medicine and Andrology Outpatient Clinic for sexual dysfunctions. MeasurementsAll patients underwent a standardized diagnostic protocol before starting any treatment. Clinical and biochemical parameters have been collected. Higher ANDROTEST score has been used as a comprehensive marker of more severe hypogonadal symptoms. Prostate-specific antigen (PSA) and haematocrit have been used as objective surrogate markers of T bioactivity. ResultsAfter adjusting for TT and lifestyle, SHBG showed a significant positive association with ANDROTEST score (B=0.79 [0.61; 0.96], P<.0001). Conversely, higher SHBG, independently of TT, was negatively related to PSA (B=-0.86 [-0.83; -0.89]; P<.0001) and haematocrit (B=-0.64 [-0.88; -0.40]; P<.0001), after adjustment for the aforementioned confounders along with age and body mass index. Furthermore, a relationship between SHBG and lipids or blood pressure was found, with lower SHBG levels associated with a worse metabolic profile, independently of TT. ConclusionsHigher SHBG, independently of TT, is associated with either subjective or objective androgen deficiency features. This indicates that besides a hypogonadism due to an impaired T production, a hypogonadism due to a lower biological activity of T does exist.